Intermittent oral trimethoprim/sulfamethoxazole on two non‐consecutive days per week is effective as Pneumocystis jiroveci pneumonia prophylaxis in pediatric patients receiving chemotherapy or hematopoietic stem cell transplantation

Abstract

Pneumocystis jiroveci pneumonia (PCP) is a serious complication in patients receiving chemotherapy or hematopoietic stem cell transplantation. Current recommendations for trimethoprim‐sulfamethoxazole (TMP‐SMZ) dosing as PCP prophylaxis in immunocompromised patients are based on either daily dosing or dosing three consecutive days per week. We report our experience of prophylaxis with TMP‐SMZ twice daily on two non‐consecutive days per week in 145 immunocompromised children with hematologic disorders, cancer, or metabolic disorders following chemotherapy or hematopoietic stem cell transplantation. There were no breakthrough cases of PCP. We therefore conclude our prophylaxis regimen is effective against PCP in immunocompromised children. Pediatr Blood Cancer 2009;52:142–144. © 2008 Wiley‐Liss, Inc.

Twice Weekly Pneumocystis jiroveci Pneumonia Prophylaxis With Trimethoprim-Sulfamethoxazole in Pediatric Patients With Acute Lymphoblastic Leukemia

“…[10][11][12] Souza et al 12 compared twice weekly TMP/SMX (TMP 160 mg/SMX 800 mg twice daily) with thrice weekly dapsone in allogeneic blood and marrow transplant recipients (neither of which is a recommended nor alternative regimen for PCP prophylaxis for ALL). They found a similar rate of PCP with twice weekly TMP/ SMX as compared with earlier studies with thrice weekly or daily TMP/SMX.…”

“…Lindemulder and Albano 10 treated pediatric leukemia and lymphoma patients with 5 mg/kg/d of TMP divided into 2 doses on 2 consecutive days. Ohata et al, 11 in contrast, used a dose of 8 mg/kg/d of TMP divided into 2 doses on 2 nonconsecutive days for children with malignancies, hematologic disorders, and metabolic disorders as well as autologous and allogeneic hematopoietic stem cell transplant recipients. They reasoned that 2 nonconsecutive days would be better tolerated than consecutive days.…”

Question 1: Co-trimoxazole dosing dilemma: what is the right dose?

“…Although myelosuppression associated with co-trimoxazole use is dose-dependent, therefore, theoretically more likely to occur with higher doses,20 this effect was not observed in our review. The study that examined 8 mg/kg/day17 on 2 days/week did not report a higher incidence of adverse effects compared with those using lower doses (5 mg/kg/day) 16. This may be partially explained by the inclusion of a high proportion of patients receiving treatment for brain and solid tumours (as opposed to haematological malignancy) in the study of 8 mg/kg/day 17.…”

“…Apart from one study,17 therapy was administered on consecutive days. A large multicentre prospective cohort study over a 3 year period compared 5 mg/kg/day on 3 days, 5 or 10 mg/kg/day on 2 days and 5 or 10 mg/kg/day on 1 day/week 14.…”

“…The study that examined 8 mg/kg/day17 on 2 days/week did not report a higher incidence of adverse effects compared with those using lower doses (5 mg/kg/day) 16. This may be partially explained by the inclusion of a high proportion of patients receiving treatment for brain and solid tumours (as opposed to haematological malignancy) in the study of 8 mg/kg/day 17. Similarly, there was no difference in the proportion of neutropenic days when continuous therapy of 150 mg/m 2 /day was compared with intermittent therapy on 3 days/week 11…”